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Edible mushroom polysaccharides (EMPs) as a natural macromolecular carbohydrate have a very complex structure and composition. EMPs are considered ideal candidates for developing healthy products and functional foods and have received significant research attention due to their unique physiological activities such as immunomodulatory, anti-inflammatory, anti-tumor/cancer, gut microbiota regulation, metabolism improvement, and nervous system protection. The structure and monosaccharide composition of edible mushroom polysaccharides have an unknown relationship with their functional activity, which has not been widely studied. Therefore, we summarized the preparation techniques of EMPs and discussed the association between functional activity, preparation methods, structure and composition of EMPs, laying a theoretical foundation for the personalized nutritional achievements of EMP. We also establish the foundation for the further investigation and application of EMPs as novel functional foods and healthy products.
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Flammulina velutipes protein hydrolysates are known for their abundant amino acids and excellent developmental values. This study aimed to identify and screen neuroprotective peptides from F. velutipes protein hydrolysates in vitro and validate the protective effects of YVYAETY on memory impairment in scopolamine-induced mice. The F. velutipes protein was hydrolyzed by simulated gastrointestinal digestion, followed by purification through ultrafiltration and gel chromatography. The fraction exhibiting the strongest neuroprotective activity was analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The main identified peptides (SDLKPADF, WNDHYY, YVYAETY, and WFHPLF) effectively mitigated excessive ROS production by increasing SOD and GSH-px activities while inhibiting cell apoptosis and mitochondrial membrane potential (MMP) collapse against oxidative stress in Aß25-35-induced HT22 cells. By molecular docking, the interaction between peptides and the active site of the Keap1-Kelch domain reveals their capacity to regulate the Keap1/Nrf2/HO-1 pathway. In vitro, the peptide YVYAETY had the best effect and can be further validated in vivo. The behavioral tests showed that YVYAETY improved scopolamine-induced cognitive impairment in mice. YVYAETY also alleviated neuron damage including neuron vacuolation and pyknotic nuclei in the hippocampus. Furthermore, it significantly inhibited oxidative stress and suppressed the activation of the Nrf2 pathway. Therefore, this study revealed that YVYAETY had the potential to serve as a novel neuroprotective agent.
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Disfunção Cognitiva , Flammulina , Fármacos Neuroprotetores , Hidrolisados de Proteína , Escopolamina , Animais , Camundongos , Escopolamina/efeitos adversos , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/química , Disfunção Cognitiva/tratamento farmacológico , Disfunção Cognitiva/induzido quimicamente , Hidrolisados de Proteína/farmacologia , Hidrolisados de Proteína/química , Flammulina/química , Masculino , Estresse Oxidativo/efeitos dos fármacos , Peptídeos/farmacologia , Peptídeos/química , Simulação de Acoplamento Molecular , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Apoptose/efeitos dos fármacosRESUMO
The tumor entrance of drug delivery systems, including therapeutic proteins and nanomedicine, plays an essential role in affecting the treatment outcome. Nanoparticle size is a critical but contradictory factor in making a trade-off among blood circulation, tumor accumulation, and penetration. Here, this work designs a series of single-molecule gadolinium (Gd)-based magnetic resonance imaging (MRI) nanoprobes with well-defined sizes to precisely explore the size-dependent tumor entrance in vivo. The MRI nanoprobes obtained by divergent synthesis contain a core molecule of macrocyclic Gd(III)-chelate and different layers of dendritic lysine units, mimicking globular protein. This work finds that the r1 relaxivity and MR imaging signals increase with the nanoparticle size. The nanoprobe with a lower limit of critical size threshold ≈8.0 nm achieves superior tumor accumulation and penetration. These single-molecule MRI nanoprobes can be served to precisely examine the size-related nanoparticle-biological interactions.
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Nanopartículas , Neoplasias , Humanos , Imageamento por Ressonância Magnética/métodos , Neoplasias/diagnóstico por imagem , Meios de ContrasteRESUMO
The active transport of nanoparticles into solid tumors through transcytosis has been recognized as a promising way to enhance tumor accumulation and penetration, but the effect of the physicochemical properties of nanoparticles remains unclear. Herein, we develop a type of single-molecule dual imaging nanodot by divergent growth of perylenediimide (PDI)-dye-cored polylysine dendrimers and internal orthogonal conjugation of Gd(III)-based macrocyclic probes for fluorescence imaging and magnetic resonance imaging (MRI) of surface chemistry-dependent tumor entrance. The MRI and fluorescence imaging show that sixth-generation nanodots with acetylated (G6-Ac) and oligo ethylene glycol (G6-OEG) surfaces exhibit similar high tumor accumulation but different intratumor distribution. Cellular uptake and transport experiments suggest that G6-Ac nanodots have lower lysosomal entrapment (61% vs. 83%) and a higher exocytotic rate (47% vs. 29%) than G6-OEG. Therefore, G6-Ac is more likely to undergo intercellular transport through cell transcytosis, and is able to reach a tumor area distant from blood vessels, while G6-OEG mainly enters the tumor through enhanced permeability and retention (EPR) effect-based passive transport, and is not able to deliver to distant tumor areas. This study suggests that it is possible to boost the tumor entrance of nanoparticles by engineering surface chemistry for active transport.
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BACKGROUND: Lead (Pb) is a highly toxic and persistent substance that easily accumulates in living organisms, eliciting cellular toxicity and oxidative stress. Some selenium-containing proteins and peptides prepared from plant extracts are beneficial for protecting the body's health and resisting external disturbances. In the present study, selenium-containing peptide species were prepared from selenium-enriched Pleurotus eryngii protein hydrolysates and to evaluate the benefits of selenium-containing peptides on Pb-induced oxidative stress in NCTC1469 hepatocytes. RESULTS: Trypsin was selected as primary enzyme to hydrolyze the selenium-enriched protein (SPH). The optimal hydrolysis conditions were: hydrolysis time, 1.5 h; initial pH 8.0. The SPH was digested by trypsin and then purified by ultrafiltration, gel filtration chromatography and reversed-phase HPLC to obtain the selenium-containing peptides SPH-I-2. Furthermore, SPH-I-2 was analyzed and a number of total 12 selenium-containing peptides were identified by liquid chromatography-tandem mass spectroscopy. The NCTC1469 cell culture study showed that selenium-containing peptides were capable of reducing reactive oxygen species levels and regulating the Keap1/Nrf2 pathway by upregulating Nrf2, HO-1, GCLC, GCLM and NQO1 genes and downregulating Keap1 genes. Moreover, selenium-containing peptides were also able to suppress Pb-induced elevated levels of nitric oxide (NO), lactate dehydrogenase (LDH), malondialdehyde (MDA), increase antioxidant enzyme activity and alleviate cell apoptosis. CONCLUSION: The present study indicated that the selenium-containing peptides could protect cells from Pb2+ -induced oxidative stress. © 2023 Society of Chemical Industry.
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Selênio , Selênio/metabolismo , Proteína 1 Associada a ECH Semelhante a Kelch/genética , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Chumbo/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Tripsina/metabolismo , Estresse Oxidativo , Antioxidantes/farmacologia , Antioxidantes/metabolismo , Peptídeos/farmacologia , Peptídeos/metabolismo , Hepatócitos/metabolismoRESUMO
This study elucidated the biosynthesis and changing behaviors of organic sulfide in shiitake mushrooms upon hot-air drying treatment. The changes of aw, moisture migration, contours of taste and flavor, organic sulfide, and 4 key enzyme activities were monitored throughout three drying procedures (CT/ST1/ST2). Results showed that drying rate was related to the moisture migration. Key enzymes of γ-GTase, ASFase and CS lyase were heat-resistant proteases, while C-Dase exhibited low thermal stability with the activity decreased during treatment. A total of 17 organic sulfides were identified and PLS analyses suggested 6 cyclic polysulfides were formed by C-Dase desulfurization, while 5 thioethers generation were related to the thermal cleavage of direct precursors (straight-chain di/tris/tetrasulfonyl esters) and Maillard reaction. These results indicated that ST2 drying procedures had a positive effect on the formation of cyclic polysulfides at the end of drying pried and the achievement of premium flavor qualities.
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Cogumelos Shiitake , Proteína 1 Semelhante a Receptor de Interleucina-1 , Sulfetos , Temperatura AltaRESUMO
Therapeutic nanoplatforms are widely used in the diagnosis and treatment of breast cancer due to the merits of enabling high soft-tissue resolution and the availability of numerous therapeutic nanoparticles. It is thus vital to develop multifunctional theranostic nanoparticles for the visualization and dynamic monitoring of tumor therapy. In this study, we designed a manganese-based and hypericin-loaded polyester dendrimer nanoparticle (MHD) for magnetic resonance imaging (MRI) and hypericin-based photodynamic therapy (PDT) enhancement. We found that MHD could greatly enhance MRI contrast with a longitudinal relaxivity of 5.8 mM-1 s-1 due to the Mn-based paramagnetic dendrimer carrier. Meanwhile, the MRI-guided PDT inhibition of breast tumors could be achieved by the hypericin-carrying MHD and further improved by Mn2+-mediated alleviation of the hypoxic microenvironment and the enhancement of cellular ROS. Besides, MHD showed excellent biocompatibility and biosafety with liver and kidney clearance mechanisms. Thus, the high efficiency in MRI contrast enhancement and excellent tumor-inhibiting effects indicate MHD's potential as a novel, stable, and multifunctional nanotheranostic agent for breast cancer.
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Neoplasias da Mama , Dendrímeros , Nanopartículas , Humanos , Feminino , Manganês , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/tratamento farmacológico , Medicina de Precisão , Poliésteres , Nanopartículas/uso terapêutico , Imageamento por Ressonância Magnética/métodos , Microambiente TumoralRESUMO
BACKGROUND: Pyrimidine metabolism is critical for tumour progression. Uridine-cytidine kinase 2 (UCK2), a key regulator of pyrimidine metabolism, is elevated during hepatocellular carcinoma (HCC) development and exhibits carcinogenic effects. However, the key mechanism of UCK2 promoting HCC and the therapeutic value of UCK2 are still undefined. The aim of this study is to investigate the potential of UCK2 as a therapeutic target for HCC. METHODS: Gene expression matrices were obtained from public databases. RNA-seq, co-immunoprecipitation and RNA-binding protein immunoprecipitation were used to determine the mechanism of UCK2 promoting HCC. Immune cell infiltration level and immune-related functional scores were evaluated to assess the link between tumour microenvironment and UCK2. RESULTS: In HCC, the expression of UCK2 was upregulated in part by TGFß1 stimulation. UCK2 promoted cell cycle progression of HCC by preventing the degradation of mTOR protein and maintaining the stability of PDPK1 mRNA. We also identified UCK2 as a novel RNA-binding protein. Downregulation of UCK2 induced cell cycle arrest and activated the TNFα/NFκB signalling pathway-related senescence-associated secretory phenotype to modify the tumour microenvironment. Additionally, UCK2 was a biomarker of the immunosuppressive microenvironment. Downregulated UCK2 induced a secretory phenotype, which could improve the microenvironment, and decreased UCK2 remodelling metabolism could lower the resistance of tumour cells to T-cell-mediated killing. CONCLUSIONS: Targeting UCK2 inhibits HCC progression and could improve the response to immunotherapy in patients with HCC. Our study suggests that UCK2 could be an ideal target for HCC.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Uridina Quinase , Humanos , Proteínas Quinases Dependentes de 3-Fosfoinositídeo , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/imunologia , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Pontos de Checagem do Ciclo Celular/genética , Pontos de Checagem do Ciclo Celular/imunologia , Imunidade/genética , Imunidade/imunologia , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/imunologia , Pirimidinas , Microambiente Tumoral , Uridina Quinase/genética , Uridina Quinase/imunologiaRESUMO
Oudemansiella raphanipies, also called "Edible Queen," is a mushroom that possesses antioxidant, anti-inflammatory, anti-bacterial, anti-tumor and immunity-enhancing properties. The present study aimed to assess the effect of O. raphanipies-derived polysaccharide (ORPS) on the progression of nonalcoholic fatty liver disease (NAFLD) in mice. We studied the structure of ORPS-1 by high-performance gel permeation chromatography (HPGPC), ion chromatography-mass spectrometry (GC-MS), and Fourier transform-infrared spectroscopy (FT-IR). ORPS-1 mainly comprised galactose, fucose, glucose, mannose, and xylose, following an 18:6:6:4:1 molar ratio. In addition, the therapeutic effect as well as a potential mechanism of ORPS-1 in the treatment of high-fat diet (HFD)-induced NAFLD were investigated. The results showed that ORPS-1 improved liver function, ameliorated liver steatosis, and reduced lipid droplet accumulation in HFD mice. A metabolomics approach with GC-MS was utilized to evaluate liver improvement by ORPS-1 treatment. Principal component analysis showed that liver metabolic profiling was significantly altered by HFD feeding or treatment with an intermediate dose of ORPS-1 in mice compared with that of control mice. By investigating the metabolic pathways with identified biomarkers, various pathways such as steroid biosynthesis, valine, leucine, and isoleucine biosynthesis, glycerol phospholipid metabolism, glyceride metabolism, and arginine and proline metabolism in HFD mice were observed to be significantly influenced by ORPS-1 treatment. The results indicate ORPS-1 metabolic effects on liver tissues, provide methods for assessing the molecular impact of ORPS-1 on NAFLD, and suggest the potential mechanism underlying its health benefits.
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Agaricales , Transtornos do Metabolismo dos Lipídeos , Hepatopatia Gordurosa não Alcoólica , Agaricales/metabolismo , Animais , Antioxidantes/farmacologia , Arginina/farmacologia , Biomarcadores/metabolismo , Dieta Hiperlipídica/efeitos adversos , Fucose/farmacologia , Galactose/efeitos adversos , Glucose/metabolismo , Glicerídeos/farmacologia , Glicerol/metabolismo , Isoleucina/farmacologia , Leucina/farmacologia , Metabolismo dos Lipídeos , Transtornos do Metabolismo dos Lipídeos/metabolismo , Fígado/metabolismo , Manose , Camundongos , Camundongos Endogâmicos C57BL , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/etiologia , Hepatopatia Gordurosa não Alcoólica/metabolismo , Fosfolipídeos/metabolismo , Polissacarídeos/metabolismo , Prolina/metabolismo , Espectroscopia de Infravermelho com Transformada de Fourier , Esteroides/metabolismo , Valina/farmacologia , Xilose/metabolismoRESUMO
The treatment of drug-resistant bacterial infections attributed to the overuse of antibiotics still remains a serious challenge globally. Herein, zwitterionic charge switchable meso-silica/polypeptide hybrid nanoparticles (MSPNs) were prepared for the synergistic chemo-photodynamic therapy in the treatment of drug-resistant bacterial infections. Subsequently, azithromycin (AZT) and methylene blue (MB) were loaded in the MSPNs to form the combined chemo-photodynamic therapeutic nanoparticles (MSPNs-AZT/MB) for the treatment of methicillin-resistant Staphylococcus aureus (MRSA). Remarkably, the as-prepared MSPNs-AZT/MB exhibited a negative surface charge of -5.2 mV at physiological pH while switching into positive surface charge of 24.7 mv in an acidic environment, leading to enhanced binding with bacterial surface. The lipase-triggered AZT release up to 77.9 % was achieved, and the loaded MB demonstrated efficient singlet oxygen (1O2) generation for photodynamic therapy. The in vitro experimental results displayed an excellent antibacterial effect against MRSA in both planktonic and biofilm phenotypes. Additionally, the as-prepared MSPNs-AZT/MB exhibited synergistic and enhanced antibacterial infection effect up to 94 % comparing to monotherapy in a mice model. Considering the above advantages, the as-prepared combined chemo-photodynamic therapeutic nanoparticles showed promising biocompatibility and clinical potential for the efficient therapy of drug-resistant bacteria.
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Staphylococcus aureus Resistente à Meticilina , Nanopartículas , Fotoquimioterapia , Infecções Estafilocócicas , Animais , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Azitromicina/farmacologia , Azitromicina/uso terapêutico , Lipase/farmacologia , Azul de Metileno/farmacologia , Camundongos , Testes de Sensibilidade Microbiana , Peptídeos/farmacologia , Peptídeos/uso terapêutico , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Dióxido de Silício/farmacologia , Oxigênio Singlete , Infecções Estafilocócicas/tratamento farmacológicoRESUMO
Recently, the stimulus-sensitive drug co-delivery system has gained increasing attentions in the clinic and exhibits improved efficiency rather than the mono-chemotherapy in anti-tumor therapy. Herein, the smart charge switchable nano-micelles (NMs) were fabricated for the endosomal escape mediated co-delivery of doxorubicin (DOX) and paclitaxel (PTX) in treatment of lung adenocarcinoma. The disulfide bonds were facilitated as the linker of the polymer backbone to achieve the redox-sensitive degradation by high intracellular GSH, and acid-liable DMMA was grafted onto DOX molecules for pH-triggered drug release under acidic tumoral microenvironment. Folic acid (FA) was utilized as targeting molecule for facilitating entry of the as prepared NMs into cancer cells. Remarkably, the as fabricated NMs exhibited surface charge-switch from negative to positive during transmitting from physiological pH to the tumor extracellular pH, which can improve the cellular internalization towards cancer cell. Subsequently, the "proton-sponge" effect mediated endosome escape of the NMs was facilitated in the acidic endo/lysosome environment. By the cell assay, the NMs possessed good biocompatibility, excellent cellular uptake, and improved inhibition rate against cancer cell. Moreover, the co-delivery of DOX/PTX exhibited synergistic and enhanced solid tumor inhibition efficiency comparing to mono-chemotherapy in A-549 tumor bearing mice model. Based on above experimental results, the as prepared drug co-delivery system showed promising biosafety and potentials for efficient lung adenocarcinoma treatment in clinic.
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Adenocarcinoma de Pulmão , Neoplasias , Adenocarcinoma de Pulmão/tratamento farmacológico , Animais , Doxorrubicina/química , Portadores de Fármacos/uso terapêutico , Sistemas de Liberação de Medicamentos/métodos , Endossomos , Concentração de Íons de Hidrogênio , Camundongos , Micelas , Neoplasias/tratamento farmacológico , Oxirredução , Paclitaxel , Microambiente TumoralRESUMO
An optical detection platform based on laser induced spectroscopy and double integrating spheres techniques was developed to obtain absorption (µa), reduced scattering coefficients (µ's) and fluorescence intensity of oil. The validation experiment carried on liquid phantoms showed that the developed system could achieve high linearity, and the results of spectra analysis indicated that the fluorescence intensity has a significant negative correlation with both µa and µ's. A total of 1620 oils with six categories were detected. The reason for the difference of fluorescence and µa spectra was analyzed by comparing the measured chlorophyll, polyphenol and α-tocopherol contents. Linear discriminant analysis combined with principal component analysis based on fluorescence and µa spectra was employed, to calibrate the AFB1 classification models. The discrimination results manifested that by integrating µa with fluorescence signal, the correct classification rate could be improved by more than 10%, and the false negative rate was greatly reduced.
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Lasers , Luz , Análise Discriminante , Óleos , Espectrometria de FluorescênciaRESUMO
Edible mushrooms have been an important part of the human diet for thousands of years, and over 100 varieties have been cultivated for their potential human health benefits. In recent years, edible mushroom polysaccharides (EMPs) have been studied for their activities against obesity, inflammatory bowel disease (IBD), and cancer. Particularly, accumulating evidence on the exact causality between these health risks and specific gut microbiota species has been revealed and characterized, and most of the beneficial health effects of EMPs have been associated with its reversal impacts on gut microbiota dysbiosis. This demonstrates the key role of EMPs in decreasing health risks through gut microbiota modulation effects. This review article compiles and summarizes the latest studies that focus on the health benefits and underlying functional mechanisms of gut microbiota regulation via EMPs. We conclude that EMPs can be considered a dietary source for the improvement and prevention of several health risks, and this review provides the theoretical basis and technical guidance for the development of novel functional foods with the utilization of edible mushrooms.
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Agaricales , Microbioma Gastrointestinal , Dieta , Disbiose , Microbioma Gastrointestinal/fisiologia , Humanos , Polissacarídeos/farmacologiaRESUMO
Flammulina velutipes has anti-inflammatory, immunomodulatory, antioxidant and many bioactive properties with high contents of carbohydrate, proteins and fibers. In this study, a novel proteoglycan with polysaccharide complexes and protein chain, named PGD1-1, was isolated from F. velutipes. The structural characteristics of PGD1-1 were then determined, and its anti-proliferation and pro-apoptotic activities against HepG-2 cells were demonstrated in vitro. Results proved that the average molecular weight of PGD1-1 was 32.71 kDa, and the carbohydrate and protein contents were 93.35 and 2.33%, respectively. The protein moiety was bonded to a polysaccharide chain via O-glycosidic linkage. The monosaccharides consisted of d-glucose, D-galactose and D-xylose in a molar ratio of 21.90:2.84:1.00. PGD1-1 significantly inhibited the proliferation of HepG-2 cells by affecting cell lipid peroxidation and nitric oxide production. In addition, PGD1-1 promoted the apoptosis of HepG-2 cells, especially the early apoptosis. These findings proved that PGD1-1 was a novel potent ingredient against the proliferation of HepG-2, which will provide a theoretical basis for the development and utilization of the functional ingredients of the F. velutipes.
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Flammulina/química , Proteoglicanas/isolamento & purificação , Proteoglicanas/farmacologia , Aminoácidos/análise , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Fenômenos Químicos , Células Hep G2 , Humanos , L-Lactato Desidrogenase/metabolismo , Malondialdeído/metabolismo , Óxido Nítrico/metabolismo , Proteoglicanas/química , Superóxido Dismutase/metabolismoRESUMO
Combined chemo-photothermal therapy of gold nanorods (GNRs) for cancer treatment shows better therapeutic efficiency than mono-chemotherapy, which has gained worldwide interests of scientists and clinician in both laboratory and clinic application. However, high cytotoxicity, declined delivery efficiency, and unsatisfactory therapy effect of the GNRs are still challenging in anti-cancer treatment. Herein, a series of pH-sensitively zwitterionic polypeptide conjugated GNRs were synthesized via a gold-thiol interaction for combination of chemo-photothermal therapy in cervical cancer treatment. The acid-labile hydrazone bond was utilized to incorporate the doxorubicin (DOX) for pH-sensitive drug release under tumoral environment. The as prepared GNRs conjugates demonstrated pH-triggered surface charge conversion from negative to positive when transporting from blood circulation to tumor extracellular environment, which can facilitate the cellular uptake via electrostatic interaction. After cellular internalization, the drug release was promoted by cleavage of the hydrazone in GNRs conjugates under cancer intracellular acid environment. As the effective near-infrared (NIR) photothermal materials, the as prepared GNRs conjugates can absorb NIR photo energy and convert it into heat under irradiation, which can efficiently kill the tumor cells. In cell assay, the GNRs conjugates displayed excellent biocompatibility against normal cell, enhanced cancer cell uptake, and remarkable cancer cell killing effects. In HeLa tumor-bearing mice, the GNRs conjugates demonstrated enhanced tumor inhibition efficacy by combination of chemo-photothermal therapy.
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Nanotubos , Neoplasias do Colo do Útero , Animais , Linhagem Celular Tumoral , Doxorrubicina/farmacologia , Feminino , Ouro , Humanos , Camundongos , Peptídeos , Fototerapia , Terapia Fototérmica , Neoplasias do Colo do Útero/terapiaRESUMO
BACKGROUND: Gut microbiota plays an indispensable role in the treatment of inflammatory bowel disease (IBD) and colitis-associated cancer (CAC). As traditional medicinal fungi, previous studies have shown that Ophiocordyceps sinensis could better maintain intestinal health via promoting the growth of probiotics in vitro compared with Cordyceps militaris. However, the detailed pharmacological activities and clinical efficacy of O. sinensis and C. militaris are still elusive. PURPOSE: We aimed to evaluate the different actions of O. sinensis and C. militaris on colitis-associated tumorigenesis in Azoxymethane (AOM)/Dextran Sulfate Sodium (DSS)-treated mice and explore the potential gut microbiota-dependent mechanisms. METHODS: C57BL/6 mice (Male, 4 weeks old) were used to construct the AOM/DSS-induced CAC mice model. The mice were administered with 0.6 mg/g/d O. sinensis or C. militaris for 12 weeks. It's worth noting that fecal microbiota transplantation (FMT) and antibiotic treatment were used to investigated the complex interactions between the medicinal fungi, gut microbiota and colonic tumorigenesis. RESULTS: O. sinensis treatment significantly increased the body weight and survival rate, reduced the number of colon tumors, improved the damage of colon epithelial tissue, restored the crypt structure and alleviate the colonic inflammation in AOM/DSS-treated mice. RT-qPCR results indicated that O. sinensis partly regulated the Wnt/ß-catenin signaling via alleviating the overexpression of ß-catenin, TCF4 and c-Myc genes in adjacent noncancerous tissues. Compared with C. militaris, O. sinensis showed better anti-tumor activity. Gut microbiota analysis revealed that O. sinensis reversed the decline of gut microbiota diversity and the structural disorder induced by AOM/DSS. Spearman's correlation analysis showed that O. sinensis promoted the growth of Parabacteroides goldsteinii and Bifidobacterium pseudolongum PV8-2, which were positively correlated with the anti-tumor activity and the production of SCFAs. FMT combined with antibiotic treatment showed that horizontal fecal transfer derived from O. sinensis-treated mice improved the intestinal inflammation and alleviated the colitis-associated tumorigenesis, which was consistent with the direct ingestion of O. sinensis. CONCLUSION: O. sinensis could better attenuate colitis-associated tumorigenesis compared with C. militaris. These effects might be at least partially due to the increased abundance of probiotics, especially P. goldsteinii and B. pseudolongum PV8-2.
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Colite , Cordyceps , Microbioma Gastrointestinal , Animais , Bacteroidetes , Bifidobacterium , Carcinogênese , Colite/induzido quimicamente , Colite/tratamento farmacológico , Cordyceps/química , Sulfato de Dextrana , Modelos Animais de Doenças , Masculino , Camundongos , Camundongos Endogâmicos C57BL , ProbióticosRESUMO
Seven enzyme groups were applied to hydrolyze broken fruiting bodies of morel mushroom (Morchella sextelata) to extract umami substances. Physical-chemical properties, as well as compositions and concentrations of quintessential umami compounds of morel hydrolysates were analyzed. Electronic tongue and electronic nose were used to evaluate the sensory characteristics. The results suggested that peptides below 3 kDa showed the highest correlation with umami taste. Morel hydrolysate obtained from Neutrase-Flavourzyme (NF) combination contained the most contents of small peptides (<3 kDa), free amino acids (224.83 ± 0.87 mg/g), as well as flavor 5'-nucleotides (4.84 ± 0.32 mg/g), giving the best overall flavor properties. The reaction conditions of NF were optimized by response surface methodology (RSM). The highest degree of hydrolysis (DH) was up to 36.64%. An enzymatic hydrolysis approach was established to develop novel flavor products with high umami and low bitter taste from morel mushroom.
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Ascomicetos/química , Enzimas/química , Aromatizantes/química , Paladar , Aminoácidos/análise , Nariz Eletrônico , Proteínas Fúngicas/química , Hidrólise , Nucleotídeos/análise , Nucleotídeos/química , Peptídeos/análise , Peptídeos/química , Hidrolisados de Proteína/químicaRESUMO
Biologically active peptides released by proteins are important in regulating immunity. The purpose of this study was to isolate and purify an immunologically active peptide from Hericium erinaceus (H. erinaceus) and to explore its effect on cytokine secretion and differentiation of macrophages. An active peptide with an amino acid sequence, Lys-Ser-Pro-Leu-Tyr (KSPLY) was obtained from H. erinaceus protein by ultrafiltration combined with multistage chromatography separation and identification technology. Subsequently, it was confirmed that the synthetic peptide KSPLY had a good immunomodulatory activity at a concentration of 100 µmol/L and could promote the secretion of NO, IL-1ß, IL-6 and TNF-α by macrophages. The effects of KSPLY on M1 macrophages and M2 macrophages were also studied. Results showed that KSPLY inhibited the secretion of NO and IL-6 by M1 macrophages and promoted the tendency of M2 macrophages to transform to M1 macrophages. Therefore, it can be concluded that KSPLY is an effective immunomodulatory peptide that may be beneficial in cancer treatment and human health improvement.
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Adjuvantes Imunológicos/farmacologia , Hericium/química , Macrófagos/efeitos dos fármacos , Oligopeptídeos/isolamento & purificação , Proteínas de Plantas/química , Animais , Polaridade Celular/efeitos dos fármacos , Concentração de Íons de Hidrogênio , Interleucina-1beta/metabolismo , Interleucina-6/metabolismo , Macrófagos/metabolismo , Camundongos , Oligopeptídeos/química , Oligopeptídeos/farmacologia , Hidrolisados de Proteína/química , Células RAW 264.7 , Fator de Crescimento Transformador alfa/metabolismoRESUMO
Soy protein isolate (SPI) is a nutritional commercial product, while the poor solubility and gelling restricts its applications for functional foods. To surmount the challenge presented by this poor solubility, the gelling polysaccharide shows potential in ameliorating SPI. In this study, SPI/Flammulina velutipes polysaccharide (FVP) hydrogels were prepared under four mixing ratios (32:1, 20:1,15:1 and 10:1, w/w) at both pH6.5 and pH3.5, respectively. The stability of hydrogels and its immunostimulatory impact on RAW264.7 cells were assessed. Initial results revealed that water holding capacity increased when increasing the mixing ratios, likely to be the results of enhanced electrostatic interaction between SPI and FVP. The addition of FVP contributed to the improved swelling ratio and lowered the degradation ratio. Such structure feature was shown to be favorable for hydrogels to culture cells. More importantly, SPI/FVP hydrogels demonstrated no cytotoxic effect on cell metabolic activity. The culture of SPI/FVP hydrogels enhanced the immunostimulatory capacity in RAW264.7 cells by increasing phagocytosis and inducing the production of pro-inflammatory cytokines. The performances of the hydrogels made at pH3.5 were superior to those prepared at pH6.5. Our results suggested SPI/FVP hydrogels may provide application potential for the development of functional foods.
Assuntos
Hidrogéis/farmacologia , Macrófagos/efeitos dos fármacos , Polissacarídeos/farmacologia , Proteínas de Soja/química , Animais , Citocinas/metabolismo , Hidrogéis/química , Concentração de Íons de Hidrogênio , Mediadores da Inflamação/metabolismo , Macrófagos/imunologia , Macrófagos/metabolismo , Camundongos , Óxido Nítrico/biossíntese , Fagocitose/efeitos dos fármacos , Polissacarídeos/química , Células RAW 264.7RESUMO
The efficient selectivity of heavy metal ions from wastewater is still challenging but gains great public attention in water treatment on a world scale. In this study, the novel disulfide cross-linked poly(methacrylic acid) iron oxide (Fe3O4@S-S/PMAA) nanoparticles with selective adsorption, improved adsorption capability, and economic reusability were designed and prepared for selective adsorption of Pb(II) ions in aqueous solution. In this study, nuclear magnetic resonance, dynamic light scattering, scanning electron microscopy, X-ray diffraction, vibrating sample magnetometry, and thermogravimetric analysis were utilized to study the chemophysical properties of Fe3O4@S-S/PMAA. The effect of different factors on adsorption properties of the Fe3O4@S-S/PMAA nanoparticles for Co(II) and Pb(II) ions in aqueous solution was explored by batch adsorption experiments. For adsorption mechanism investigation, the adsorption of Fe3O4@S-S/PMAA for Co(II) and Pb(II) ions can be better fitted by a pseudo-second-order model, and the adsorption process of Fe3O4@S-S/PMAA for Co(II) and Pb(II) matches well with the Freundlich isotherm equation. Notably, in the adsorption experiments, the Fe3O4@S-S/PMAA nanoparticles were demonstrated to have a maximum adsorption capacity of 48.7 mg·g-1 on Pb(II) ions with a selective adsorption order of Pb2+ > Co2+ > Cd2+ > Ni2+ > Cu2+ > Zn2+ > K+ > Na+ > Mg2+ > Ca2+ in the selective experiments. In the regeneration experiments, the Fe3O4@S-S/PMAA nanoparticles could be easily recovered by desorbing heavy metal ions from the adsorbents with eluents and showed good adsorption capacity for Co(II) and Pb(II) after eight recycles. In brief, compared to other traditional nanoadsorbents, the as-prepared Fe3O4@S-S/PMAA with improved adsorption capability and high regeneration efficiency demonstrated remarkable affinity for adsorption of Pb(II) ions, which will provide a novel technical platform for selective removal of heavy metal ions from actual polluted water.